Most of our daily activities are performed under light levels where our vision is based on cone photoreceptors. Our long term goal is to contribute to an understanding of the basic mechanisms underlying cone-based vision, how these mechanisms are disrupted in vision disorders and how vision loss might be prevented or reversed. For this application a multidisciplinary approach using psychophysics, adaptive optics imaging, electrophysiology, and molecular biology will be used to address three specific aims: Specific Aim 1. Identify variations linked to the X-chromosome cone photopigment gene array that are associated with shifts in the relative numbers of human L and M cones. There is astounding individual variation in the L:M cone ratio among humans with normal color vision. To test hypotheses about the mechanism responsible for determining whether a cone is M or L, the region of the X-chromosome containing the cone photopigment genes will be examined in a large sample of males with normal color vision who have known differences in the ratio of L:M cones. Specific Aim 2. Determine the consequences for the human cone mosaic of identified genetic differences that are proposed to affect the photoreceptor topography. Adaptive optics imaging coupled with retinal densitometry will be used to visualize structural and functional changes in the cone photoreceptors and their topographical arrangement in the retina as the result of genetic mutations. Specific Aim 3. Explore an amazing plastic neural mechanism that is hypothesized to allow information from the environment to instructively reorganize neural connections throughout life. We will characterize a recently discovered plasticity of the adult visual system in which the long term effects of altered chromatic experience have been found to change the color vision of adults. This will allow hypotheses about the role of neural plasticity in establishing and maintaining proper function of the visual system to be tested.